Individuals with Metabolic Syndrome Show Altered Fecal Lipidomic Profiles with No Signs of Intestinal Inflammation or Increased Intestinal Permeability

Authors

Mia J. Coleman, University of New Mexico School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Luis M. Espino, University of New Mexico School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Hernan Lebensohn, University of New Mexico School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Marija V. Zimkute, Clinical and Translational Science Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
Negar Yaghooti, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Christina L. Ling, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Jessica M. Gross, Clinical and Translational Science Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
Natalia Listwan, Clinical and Translational Science Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
Sandra Cano, Clinical and Translational Science Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
Vanessa Garcia, Clinical and Translational Science Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
Debbie M. Lovato, Clinical and Translational Science Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
Susan L. Tigert, Clinical and Translational Science Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
Drew R. Jones, Metabolomics Core Resource Laboratory, New York University Langone Health, New York, NY 10016, USA.
Rama R. Gullapalli, 5 Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Neal E. Rakov, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Euriko G. Torrazza Perez, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Eliseo F Castillo, Clinical and Translational Science Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.

Document Type

Article

Publication Date

5-11-2022

Abstract

BACKGROUND: Metabolic Syndrome (MetS) is a clinical diagnosis where patients exhibit three out of the five risk factors: hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, hyperglycemia, elevated blood pressure, or increased abdominal obesity. MetS arises due to dysregulated metabolic pathways that culminate with insulin resistance and put individuals at risk to develop various comorbidities with far-reaching medical consequences such as non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease. As it stands, the exact pathogenesis of MetS as well as the involvement of the gastrointestinal tract in MetS is not fully understood. Our study aimed to evaluate intestinal health in human subjects with MetS.

METHODS: We examined MetS risk factors in individuals through body measurements and clinical and biochemical blood analysis. To evaluate intestinal health, gut inflammation was measured by fecal calprotectin, intestinal permeability through the lactulose-mannitol test, and utilized fecal metabolomics to examine alterations in the host-microbiota gut metabolism.

RESULTS: No signs of intestinal inflammation or increased intestinal permeability were observed in the MetS group compared to our control group. However, we found a significant increase in 417 lipid features of the gut lipidome in our MetS cohort. An identified fecal lipid, diacyl-glycerophosphocholine, showed a strong correlation with several MetS risk factors. Although our MetS cohort showed no signs of intestinal inflammation, they presented with increased levels of serum TNFα that also correlated with increasing triglyceride and fecal diacyl-glycerophosphocholine levels and decreasing HDL cholesterol levels.

CONCLUSION: Taken together, our main results show that MetS subjects showed major alterations in fecal lipid profiles suggesting alterations in the intestinal host-microbiota metabolism that may arise before concrete signs of gut inflammation or intestinal permeability become apparent. Lastly, we posit that fecal metabolomics could serve as a non-invasive, accurate screening method for both MetS and NAFLD.

Recommended Citation

Coleman MJ, Espino LM, Lebensohn H, Zimkute MV, Yaghooti N, Ling CL, Gross JM, Listwan N, Cano S, Garcia V, Lovato DM, Tigert SL, Jones DR, Gullapalli RR, Rakov NE, Torrazza Perez EG, Castillo EF. Individuals with Metabolic Syndrome Show Altered Fecal Lipidomic Profiles with No Signs of Intestinal Inflammation or Increased Intestinal Permeability. Metabolites. 2022 May 11;12(5):431. doi: 10.3390/metabo12050431. PMID: 35629938; PMCID: PMC9143200.